A global sampling approach to designing and reengineering RNA secondary structures.

Alex Levin 1, 2 Mieszko Lis 1 Yann Ponty 3, 4 Charles W O'Donnell 1 Srinivas Devadas 1 Bonnie Berger 1, 2 Jérôme Waldispühl 1, 2, 5
4 AMIB - Algorithms and Models for Integrative Biology
CNRS - Centre National de la Recherche Scientifique : UMR8623, X - École polytechnique, Inria Saclay - Ile de France, UP11 - Université Paris-Sud - Paris 11, LRI - Laboratoire de Recherche en Informatique, LIX - Laboratoire d'informatique de l'École polytechnique [Palaiseau]
Abstract : The development of algorithms for designing artificial RNA sequences that fold into specific secondary structures has many potential biomedical and synthetic biology applications. To date, this problem remains computationally difficult, and current strategies to address it resort to heuristics and stochastic search techniques. The most popular methods consist of two steps: First a random seed sequence is generated; next, this seed is progressively modified (i.e. mutated) to adopt the desired folding properties. Although computationally inexpensive, this approach raises several questions such as (i) the influence of the seed; and (ii) the efficiency of single-path directed searches that may be affected by energy barriers in the mutational landscape. In this article, we present RNA-ensign, a novel paradigm for RNA design. Instead of taking a progressive adaptive walk driven by local search criteria, we use an efficient global sampling algorithm to examine large regions of the mutational landscape under structural and thermodynamical constraints until a solution is found. When considering the influence of the seeds and the target secondary structures, our results show that, compared to single-path directed searches, our approach is more robust, succeeds more often and generates more thermodynamically stable sequences. An ensemble approach to RNA design is thus well worth pursuing as a complement to existing approaches. RNA-ensign is available at http://csb.cs.mcgill.ca/RNAensign.
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Article dans une revue
Nucleic Acids Research, Oxford University Press, 2012, 40 (20), pp.10041-10052. 〈10.1093/nar/gks768〉
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Soumis le : jeudi 20 septembre 2012 - 10:44:14
Dernière modification le : jeudi 12 avril 2018 - 01:47:12

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Alex Levin, Mieszko Lis, Yann Ponty, Charles W O'Donnell, Srinivas Devadas, et al.. A global sampling approach to designing and reengineering RNA secondary structures.. Nucleic Acids Research, Oxford University Press, 2012, 40 (20), pp.10041-10052. 〈10.1093/nar/gks768〉. 〈hal-00733924〉

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